Advances in Engineering Venous Valves: The Pursuit of a Definite Solution for Chronic Venous Disease.

Native venous valves enable proper return of blood to the heart. Under pathological conditions (e.g., chronic venous insufficiency), venous valves malfunction and fail to prevent backward flow. Clinically, this can result in painful swelling, varicose veins, edema, and skin ulcerations leading to a chronic wound situation. Surgical correction of venous valves has proven to drastically reduce these symptoms. However, the absence of intact leaflets in many patients limits the applicability of this strategy. In this context, the development of venous valve replacements represents an appealing approach. Despite acceptable results in animal models, no venous valve has succeeded in clinical trials, and so far no single prosthetic venous valve is commercially available. This calls for advanced materials and fabrication approaches to develop clinically relevant venous valves able to restore natural flow conditions in the venous circulation. In this study, we critically discuss the approaches attempted in the last years, and we highlight the potential of tissue engineering to offer new avenues for valve fabrication. Impact statement Venous valves prosthesis offer the potential to restore normal venous flow, and to improve the prospect of patients that suffer from chronic venous disease. Current venous valve replacements are associated with poor outcomes. A deeper understanding of the approaches attempted so far is essential to establish the next steps toward valve development, and importantly, tissue engineering constitutes a unique toolbox to advance in this quest.